tbuckley/cabot-search huggingface dataset:
Health Digital Twins, Legal Liability, and Medical Practice
Authors: Andreas Kuersten
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Epistemic Rights and Responsibilities of Digital Simulacra for Biomedicine Notes1 Mechanistic methods process information according to rules established by programmers based on prior knowledge of objects and systems, whereas machine learning methods process information according to rules that they more-or-less independently develop by identifying relationships and correlations in training data.2 It is debatable whether these systems would be HDTs since they would not involve real-time data exchange with subjects. A digital representation of subjects’ past states would be generated up to the point that actual interventions were implemented, then alternative courses of action could be simulated for comparison. Since these systems would involve virtually rendering subjects’ (past) physical states, this commentary uses the term HDT to describe them.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Accommodating Aid-in-Dying Safeguards for Patients with Neurologic Disease
Authors: David Orentlicher
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on DisabilityThis article is referred to by:Permit Assisted Self-Administration: A Response to Open Peer Commentaries on Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on Disability DISCLOSURE STATEMENTThe author is working with Compassion & Choices on an update to their clinical guidelines for medical aid in dying, and is also worked with them on a legislative proposal for aid in dying in Nevada during the 2023 legislative session.Notes1 David Orentlicher, Matters of Life and Death (Princeton, NJ: Princeton University Press, 2001).2 The other main category of controversial cases has involved patients who clearly lacked decision-making capacity, whether because of youthful age or because their illness had deprived them of decision-making capacity.3 Rachel Aviv, The Death Treatment, The New Yorker, June 22, 2015, Who Has the Right to a Dignified Death? | The New Yorker; Carlo Martuscelli, Human Rights Court Sides with Belgium in Euthanasia Case, Politico, October 4, 2022, Human rights court sides with Belgium in euthanasia case – POLITICO.4 The Death Interviews, The Kevorkian Verdict, Frontline, May 14, 1996, Interviews | The Kevorkian Verdict | FRONTLINE | PBS.5 The Suicide Plan, Frontline, November 13, 2012, transcript at The Suicide Plan | FRONTLINE (pbs.org).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
In Their Own Image: Ethical Implications of the Rise of Digital Twins/Clones/Simulacra in Healthcare
Authors: Benjamin Amram, Uri Klempner, Yehuda Leibler, Dov Greenbaum
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Epistemic Rights and Responsibilities of Digital Simulacra for Biomedicine Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Digital Simulacra and the Call for Epistemic Responsibility: An Ubuntu Perspective
Authors: Brandon Ferlito, Michiel De Proost
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Epistemic Rights and Responsibilities of Digital Simulacra for Biomedicine Additional informationFundingThis work was supported by the H2020 European Research Council (grant number 949841).
The Importance of Self-Administration of Aid-in-Dying Medication
Authors: Neil Wenger
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on DisabilityThis article is referred to by:Permit Assisted Self-Administration: A Response to Open Peer Commentaries on Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on Disability DISCLOSURE STATEMENTNo potential conflict of interest was reported by the authors.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Epistemic Value of Digital Simulacra for Patients
Authors: Eleanor Gilmore-Szott
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Epistemic Rights and Responsibilities of Digital Simulacra for Biomedicine Notes1 Experiential understanding parallels objectual understanding. For more discussion see Wilkenfeld (Citation2021).2 There are a variety of different types of epistemic risk relevant to this discussion, for representational risk see Harvard and Winsberg (Citation2022). For more detail on inductive risk in AI/ML see Biddle (Citation2022) and Sullivan (Citation2022b).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
MAID in America: Expanding Our Gaze on the Ethics of Assistance
Authors: Mara Buchbinder
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on DisabilityThis article is referred to by:Permit Assisted Self-Administration: A Response to Open Peer Commentaries on Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on Disability Notes1 See Buchbinder (Citation2018) and Buchbinder (Citation2021, Chapter 6) for further discussion of this case.2 Montana, which has no regulatory statute for MAID, is an exception.Additional informationFundingThis work was supported by Greenwall Foundation and The National Science Foundation (no. 1630010).
Can People Work Together to Create a Self-Administered Act? No. Should They Work Together to Repeal the End of Life Option Act? Yes
Authors: Adam Omelianchuk
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on DisabilityThis article is referred to by:Permit Assisted Self-Administration: A Response to Open Peer Commentaries on Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on Disability Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Preventing the Slide down the Slippery Slope from Assisted Suicide to Euthanasia While Protecting the Rights of People with Disabilities Who Are “Not Dead Yet.”
Authors: George J. Annas, Heidi B. Kummer
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on DisabilityThis article is referred to by:Permit Assisted Self-Administration: A Response to Open Peer Commentaries on Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on Disability DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Digital Simulacra Mark an Ontological Shift in Biomedicine with Far-Reaching Consequences for Real Patients
Authors: Hazar Haidar, Luyba Encheva, Kalina Kamenova
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Epistemic Rights and Responsibilities of Digital Simulacra for Biomedicine Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Enabling the Nonhypothesis-Driven Approach: On Data Minimalization, Bias, and the Integration of Data Science in Medical Research and Practice
Authors: C. W. Safarlou, M. van Smeden, R. Vermeulen, K. R. Jongsma
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Epistemic Rights and Responsibilities of Digital Simulacra for Biomedicine Notes1 To make the central point of our paper, our preferred term is nonhypothesis-driven approach. But such an approach can go by many other names: data-driven, big data, agnostic, unbiased, untargeted, hypothesis-free, or holistic. When intended to (later on) generate hypotheses and/or identify causal connections, it can also be called: discovery-based, discovery-driven, exploratory, or hypothesis-generating.2 Arguably, collecting as much data as possible could lower the total amount of data generated in the long run (and save research costs) if such data can be repurposed for different studies. Relatedly, on the other hand, if bodily materials or exposure samplers such as silicone wristbands are gathered and stored in biobanks, then they can be retested with targeted high-resolution mass spectrometry methods for more specific data (Chung et al. Citation2021).3 For other (arguably derivative) biases/errors that can be reduced/eliminated by such an approach, see the discussion of false positives, publication bias, and more, in (Chung et al. Citation2021). Also, with respect to cognitive bias, such an approach affords the elimination of confirmation bias (and the identification of confounders) to the extent to which confirmation bias affects variable selection. For an overview of discussions of statistical bias, 'normative' bias, and how these two interact with each other, see (Safarlou et al. Citation2023).4 Note that we do not exhaustively discuss all positive (or potentially negative) ethical and epistemic aspects of the nonhypothesis-driven approach in this commentary. For example, we leave aside the tradeoff between coverage and sensitivity/specificity when choosing to gather data via untargeted instead of targeted high-resolution mass spectrometry (Chung et al. Citation2021).5 Cho and Martinez-Martin make a related point when mentioning "convenience sampling" and "convenience samples" (Cho and Martinez-Martin Citation2023).6 We would like to thank Stefan Gaillard, Salome Kakhaia, and our colleagues from Bioethics & Health Humanities, for their constructive feedback.Additional informationFundingCS, RV and KJ acknowledge financial support by the EXPANSE project funded by the European Union's Horizon 2020 research and innovation program under grant agreement number 874627. In addition, RV acknowledges funding by the Gravitation program of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research under NWO grant number 024.004.017.
What Does True Equality in Assisted Dying Require?
Authors: Scott Y. H. Kim
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on Disability DISCLAIMERThe opinions expressed are the authors, and do not represent the views of the NIH, DHHS, or the US government.Notes1 I will use "assisted dying" as a general term to cover intentional termination of human life that requires the involvement of another (i.e., medical assistance in dying, euthanasia, assisted suicide, physician-assisted suicide, physician aid in dying, etc.).2 This moral sense seems to have a long evolutionary history, as even some birds apparently know when they are being treated unfairly. See Wascher (Citation2017). Animals know when they are being treated unfairly (and they don't like it). The Conversation. http://theconversation.com/animals-know-when-they-are-being-treated-unfairly-and-they-dont-like-it-73152. For the purposes of this essay, I use "fairness," "parity," "equality," and "non-discrimination" interchangeably.3 "[Booth Gardner, former governor of Washington and advocate for legalized assisted death] sees [a restrictive law] as a first step. If he can sway Washington to embrace a restrictive law, then other states will follow. And gradually, he says, the nation's resistance will subside, the culture will shift and laws with more latitude will be passed…" quoted in: Daniel, Bergner. Citation2007. Death in the family. NYT Magazine, December 2. See also: Jones, R. P. Citation2007. Liberalism's troubled search for equality. Notre Dame, IN: University of Notre Dame Press. See especially p. 77ff for a historical discussion of this strategy in the passage of Oregon assisted dying law.4 Canada is the best example of expansion of categories, going from a prohibition to the boundary of reasonably foreseeable natural death to the erasure of that boundary in a matter of few years. But we could also point to the Netherlands, where psychiatric EAS was introduced some years after the courts effectively decriminalized EAS, the subsequent expansions in meaning of what is medically based suffering, along with the perennial pressure to legalize EAS for those "tired of living." See Kim (Citation2022) and also Florijn, B. W. (Citation2018). Extending' euthanasia to those 'tired of living' in the Netherlands could jeopardize a well-functioning practice of physicians' assessment of a patient's request for death. Health Policy 122(3): 315–9. Of course, it is true that US states have maintained the terminal illness condition for 30 years, but I remind the reader to the preceding footnote and the fact of this AJOB target article.5 Paragraph 7, General Comment 1 states: "[Substitute decision-making regimes] … must be abolished in order to ensure that full legal capacity is restored to persons with disabilities on an equal basis with others."Additional informationFundingThe author is funded by the Intramural Research Program, NIH, CL010539.
Integrating Social Determinants of Health into Ethical Digital Simulations
Authors: Kristin Kostick-Quenet, Vasiliki Rahimzadeh, Sharmila Anandasabapathy, Meghan Hurley, Anika Sonig, Amy Mcguire
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Epistemic Rights and Responsibilities of Digital Simulacra for Biomedicine Additional informationFundingThis work was supported by National Center for Advancing Translational Sciences (grant number: R01TR004243).
When Anti-Discrimination Discriminates
Authors: Harold Braswell, Rosemarie Garland-Thomson
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on Disability DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
TREM1 activation of myeloid cells promotes antitumor immunity
Authors: Vladislava Juric, Erin Mayes, Mikhail Binnewies, Tian Lee, Pamela Canaday, Joshua L. Pollack, Joshua Rudolph, Xiaoyan Du, Victoria M. Liu, Subhadra Dash, Rachael Palmer, Nadine S. Jahchan, Åsa Johanna Ramoth, Sergio Lacayo, Shilpa Mankikar, Manith Norng, Chris Brassell, Aritra Pal, Christopher Chan, Erick Lu, Venkataraman Sriram, Michel Streuli, Matthew F. Krummel, Kevin P. Baker, Linda Liang
Journal: Science Translational Medicine (2023)

Myeloid cells in the tumor microenvironment (TME) can exist in immunosuppressive and immunostimulatory states that impede or promote antitumor immunity, respectively. Blocking suppressive myeloid cells or increasing stimulatory cells to enhance antitumor immune responses is an area of interest for therapeutic intervention. Triggering receptor expressed on myeloid cells-1 (TREM1) is a proinflammatory receptor that amplifies immune responses. TREM1 is expressed on neutrophils, subsets of monocytes and tissue macrophages, and suppressive myeloid populations in the TME, including tumor-associated neutrophils, monocytes, and tumor-associated macrophages. Depletion or inhibition of immunosuppressive myeloid cells, or stimulation by TREM1-mediated inflammatory signaling, could be used to promote an immunostimulatory TME. We developed PY159, an afucosylated humanized anti-TREM1 monoclonal antibody with enhanced FcγR binding. PY159 is a TREM1 agonist that induces signaling, leading to up-regulation of costimulatory molecules on monocytes and macrophages, production of proinflammatory cytokines and chemokines, and enhancement of T cell activation in vitro. An antibody against mouse TREM1, PY159m, promoted antitumor efficacy in syngeneic mouse tumor models. These results suggest that PY159-mediated agonism of TREM1 on tumoral myeloid cells can promote a proinflammatory TME and offer a promising strategy for immunotherapy.
An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models
Authors: Emiko Urano, Yumi Itoh, Tatsuya Suzuki, Takanori Sasaki, Jun-ichi Kishikawa, Kanako Akamatsu, Yusuke Higuchi, Yusuke Sakai, Tomotaka Okamura, Shuya Mitoma, Fuminori Sugihara, Akira Takada, Mari Kimura, Shuto Nakao, Mika Hirose, Tadahiro Sasaki, Ritsuko Koketsu, Shunya Tsuji, Shota Yanagida, Tatsuo Shioda, Eiji Hara, Satoaki Matoba, Yoshiharu Matsuura, Yasunari Kanda, Hisashi Arase, Masato Okada, Junichi Takagi, Takayuki Kato, Atsushi Hoshino, Yasuhiro Yasutomi, Akatsuki Saito, Toru Okamoto
Journal: Science Translational Medicine (2023)

The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron subvariants display further immune evasion and antibody escape. An engineered angiotensin-converting enzyme 2 (ACE2) decoy composed of high-affinity ACE2 and an IgG1 Fc domain could offer an alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum and therapeutic potential in rodent models. Here, we demonstrate that the engineered ACE2 decoy retains neutralization activity against Omicron subvariants, including the currently emerging XBB and BQ.1 strains, which completely evade antibodies currently in clinical use. SARS-CoV-2, under the suboptimal concentration of neutralizing drugs, generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against the engineered ACE2 decoy. Furthermore, inhalation of aerosolized decoys improved the outcomes of rodents infected with SARS-CoV-2 at a 20-fold lower dose than that of intravenous administration. Last, the engineered ACE2 decoy exhibited therapeutic efficacy for cynomolgus macaques infected with SARS-CoV-2. These results indicate that this engineered ACE2 decoy represents a promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation could be considered as a noninvasive approach to enhance the efficacy of COVID-19 treatments.
Perirenal Adipose Tissue Is Associated With Renal Dysfunction and Abnormal Hemodynamics in Patients With HFpEF
Authors: Eva M. Boorsma, Hidemi Sorimachi, Jozine M. ter Maaten, Dirk J. van Veldhuisen, Kazunori Omote, Naoki Takahashi, Jeffrey M. Testani, Tineke P. Willems, Adriaan A. Voors, Barry A. Borlaug
Journal: JACC Heart Failure (2023)
Farnesol prevents aging-related muscle weakness in mice through enhanced farnesylation of Parkin-interacting substrate
Authors: Ju-Hyeon Bae, Areum Jo, Sung Chun Cho, Yun-Il Lee, Tae-In Kam, Chang-Lim You, Hyeon-Ju Jeong, Hyebeen Kim, Myong-Ho Jeong, Yideul Jeong, Young Wan Ha, Yu Seon Kim, Jiwoon Kim, Seung-Hwa Woo, Minseok S. Kim, Eui Seok Shin, Sang Ok Song, Hojin Kang, Rin Khang, Soojeong Park, Joobae Park, Valina L. Dawson, Ted M. Dawson, Sang Chul Park, Joo-Ho Shin, Jong-Sun Kang
Journal: Science Translational Medicine (2023)

Peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis. Reduced PGC-1α abundance is linked to skeletal muscle weakness in aging or pathological conditions, such as neurodegenerative diseases and diabetes; thus, elevating PGC-1α abundance might be a promising strategy to treat muscle aging. Here, we performed high-throughput screening and identified a natural compound, farnesol, as a potent inducer of PGC-1α. Farnesol administration enhanced oxidative muscle capacity and muscle strength, leading to metabolic rejuvenation in aged mice. Moreover, farnesol treatment accelerated the recovery of muscle injury associated with enhanced muscle stem cell function. The protein expression of Parkin-interacting substrate (PARIS/ Zfp746 ), a transcriptional repressor of PGC-1α, was elevated in aged muscles, likely contributing to PGC-1α reduction. The beneficial effect of farnesol on aged muscle was mediated through enhanced PARIS farnesylation, thereby relieving PARIS-mediated PGC-1α suppression. Furthermore, short-term exercise increased PARIS farnesylation in the muscles of young and aged mice, whereas long-term exercise decreased PARIS expression in the muscles of aged mice, leading to the elevation of PGC-1α. Collectively, the current study demonstrated that the PARIS–PGC-1α pathway is linked to muscle aging and that farnesol treatment can restore muscle functionality in aged mice through increased farnesylation of PARIS.
Biomechanics and situational patterns associated with anterior cruciate ligament injuries in the National Basketball Association (NBA)
Authors: Vikram S Gill, Sailesh V Tummala, Sayi P Boddu, Joseph C Brinkman, Kade S McQuivey, Anikar Chhabra
Journal: British Journal of Sports Medicine (2023)

Objectives Perform a comprehensive video analysis of all anterior cruciate ligament (ACL) injuries in National Basketball Association (NBA) athletes from 2006 to 2022 to determine the associated biomechanics, injury mechanism and game situation. Methods NBA players diagnosed with an ACL tear from 2006 to 2022 were identified and videos of each injury evaluated by two reviewers. Visual evaluation included assessment of joint kinematics at three time points: initial contact of the injured leg with the ground (IC), 33 milliseconds later (IC+33) and 66 milliseconds later (IC+66). Game situation was assessed qualitatively. Results Videos of 38 out of 47 (80.9%) ACL tears were obtained. 9 injuries were non-contact, while 29 involved indirect contact. Between IC and IC+33, average knee valgus increased from 5.1° to 12.0° and knee flexion increased from 12.6° to 32.6°. At all time points, the majority of injuries involved trunk tilt and rotation towards the injured leg, hip abduction and neutral foot rotation. The most common game situations for injury included the first step when attacking the basket following picking up the ball (n=13), landing following contact in the air (n=11) and jump stop (n=5). Conclusion Three major mechanisms predominate ACL tears in NBA players: the first step following picking up the ball when attacking, landing and jump stops. None of the injuries reviewed demonstrated direct contact to the knee, emphasising the importance of body kinematics in this injury pattern. The increase in knee valgus and knee flexion between IC and IC+33 should be noted as a possible precipitant to injury.